Chronic pain syndromes, depression (DEP) and post-traumatic stress disorder (PTSD) are associated with attentional and cognitive dysfunction, leading to excessive loss of function at work and in daily life. The overall goals of this study are to 1)develop and implement a comprehensive assessment of specific levels of the neuraxis in order to pinpoint the location(s) of attentional and cognitive dysregulation in patients who have chronic low back pain (CLBP) only or CLBP and either major depressive disorder (DEP), or PTSD; and 2) to assess strategies to restore those deficits. We will be able to detect the location of disturbances at specific levels of the neuraxis: brainstem-thalamus (pre-attentional processes, using the P50 potential), thalamo-cortical (attentional processes using a psychomotor vigilance task [PVT]), cortical and hippocampal (cognition and memory processes using an operant test battery [OTB]), and relative frontal lobe blood flow (higher cognitive and critical judgment assessed with near infrared spectroscopy [NIRS]). We will then use this established paradigm to assess function at each of these levels of the neuraxis of patients with CLBP, in which cognitive impairment may be at the root of their symptoms. Our preliminary findings are the first to demonstrate the presence of a decrease in habituation of the P50 potential in patients with CLBP and DEP. This work will fill a critical void in the literature that will inform clinicians and researchers about etiology, localization of disturbed systems, potential mechanisms of action and co-morbidities that can contribute to CLBP. To our knowledge, no study has been done in patients with CLBP with and without DEP or PTSD using quantitative physiological measures that can be correlated to subjective measures (e.g. questionnaires). The proposed research will be a prospective study in patients with CLBP with and without DEP or PTSD and patients with either DEP or PTSD, as well as normal control subjects. The questionnaires include the McGill Pain Questionnaire-Short Form; Medical Outcomes Study General Health Survey-Short Form; Beck Depression Inventory; and Clinician Administered PTSD Scale. Subjects will be tested at baseline, undergo treatment with Physical Therapy and anti-depressant medication as indicated, and reassessed using physiological and questionnaire measures. The proposed research will provide the basis for an independent research career. This Project is designed to take advantage of the excellent mentoring skills of established, nationally recognized researchers. These studies will form a hub for collaborative research, bringing the Central Arkansas Veterans Healthcare System, UAMS and the GCRC investigators and facilities to bear on critical healthcare problems, CLBP, DEP and PTSD.